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关节内纳米粒中卡洛芬体内药代动力学评价在兔体内的研究:群体建模方法。

In vivo pharmacokinetic evaluation of carprofen delivery from intra-articular nanoparticles in rabbits: A population modelling approach.

机构信息

Department of Pharmacy and Pharmaceutical technology and Physical-Chemistry, Faculty of Pharmacy and Food sciences, University of Barcelona, ES, Spain; Department of Veterinary Medicine and Zootechnic, Faculty of Agricultural Sciences, University of Applied and Environmental Sciences (U.D.C.A.), Bogotá, CO, Colombia.

Department of Pharmacy and Pharmaceutical technology and Physical-Chemistry, Faculty of Pharmacy and Food sciences, University of Barcelona, ES, Spain.

出版信息

Res Vet Sci. 2021 Jul;137:235-242. doi: 10.1016/j.rvsc.2021.05.012. Epub 2021 May 21.

Abstract

Osteoarthritis is treated with COX or fosfolipase A2 inhibitors such as carprofen, a propionic acid NSAID. The enhancement of its action over the articular cartilage is mandatory to facilitate its therapeutic application. Drug uptake into the cartilage requires high synovial fluid concentrations, anticipating its rapid distribution towards bloodstream. Thus, intraarticular administration improves local targeting of the drug, lining with the site of action. A pharmacokinetic study in rabbits has been performed to evaluate carprofen nanoparticles after intraarticular administration. Pharmacokinetic analysis of plasma profiles through a modelling approach, has demonstrated the rapid distribution of drug outside of synovial chamber but mainly remaining in plasma. The data modelling has demonstrated the existence of two release-absorption processes when the nanoparticles are administered in the synovial space. Additionally, results are predictive of the PK profile of some other species such as cat, dogs or humans.

摘要

骨关节炎的治疗采用 COX 或磷酸脂酶 A2 抑制剂,如卡洛芬,一种丙酸类 NSAID。为了促进其治疗应用,必须增强其对关节软骨的作用。药物进入软骨需要高的滑液浓度,以预期其快速分布到血液中。因此,关节内给药可以改善药物的局部靶向性,与作用部位一致。已经在兔中进行了一项药代动力学研究,以评估关节内给予卡洛芬纳米粒后的情况。通过建模方法对血浆谱进行药代动力学分析,表明药物在滑膜室外迅速分布,但主要仍留在血浆中。数据模型表明,当纳米颗粒在滑膜腔内给药时,存在两种释放-吸收过程。此外,这些结果可预测其他一些物种(如猫、狗或人类)的 PK 特征。

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